Endothelial function in hypertension: role of gender.

Endothelium plays an important role in the modulation of vascular tone and structure mainly through the production of nitric oxide (NO), which causes local vasodilation and counteracts processes leading to atherothrombosis. A dysfunctioning endothelium, characterized by reduced NO availability owing to impairment of the L-arginine-NO pathway and, above all, to production of oxygen free radicals, can impair local vasomotion and promote the development of atherosclerosis and of atherothrombotic vascular events. Aging is associated with endothelial dysfunction both in normotensive subjects and in hypertensive patients, and hypertension seems to induce earlier onset of those mechanisms (i.e. impairment of the L-arginine-NO pathway and oxidative stress) that cause age-related endothelial dysfunction. Premenopausal normotensive women are protected against the deleterious effect of aging on endothelial function, and age-related impairment of endothelial function is attenuated in premenopausal hypertensive women. This protective effect on endothelial function seems to be mediated by endogenous estrogen, which preserves NO availability by activating the L-arginine-NO pathway in normotensive women and, again, by activating this pathway but above all by inhibiting oxidative stress in hypertensive women. Thus, the protective effect of endogenous estrogen on endothelial function could be a plausible mechanism contributing to the lower cardiovascular risk of premenopausal women. Finally, whether endogenous androgen can impair endothelial function is still an unsolved issue since data concerning the effect of testosterone on endothelial function are scanty and contradictory